On 12 February 2016, the Patents Court (Arnold J) granted Actavis a declaration of non-infringement in respect of the UK, French, Italian and Spanish designations of Eli Lilly’s patent EP 1 313 508 (EP 508), allowing Actavis to launch its pemetrexed diacid product in each of these countries. EP 508 relates to the use of pemetrexed disodium, which is a chemotherapeutic treatment for lung cancer, in combination with vitamin B12 and optionally a folic protein binding agent. The case was on remittal to the Patents Court to deal with the specific circumstances in which the Actavis pemetrexed product was sold with instructions that it be reconstituted with dextrose solution.

Background

This judgment is the latest instalment in a long-running dispute which began in July 2012 when Actavis brought a claim before the English Court for declarations of non-infringement (DNIs) under not only the UK designation of Eli Lilly’s European Patent, but also under the French, German, Italian and Spanish designations. Following an unsuccessful challenge to the English Court’s jurisdiction, brought by Eli Lilly, the substantive claim was heard by Arnold J at first instance in April 2014. Eli Lilly alleged direct and indirect infringement by Actavis, arguing that pemetrexed dipotassium, pemetrexed diacid or pemetrexed ditromethamine (the products in respect of which Actavis sought DNIs) would either be directly within the scope of the claim based on equivalence, or would indirectly infringe when sold in lyophilised form, by constituting an essential means for putting the invention into effect when reconstituted and/or diluted with saline (resulting in the generation of sodium ions and pemetrexed ions). Arnold J held that none of Actavis’ proposed products for which they sought DNIs would infringe EP 508 and that Actavis was entitled to a DNI in each jurisdiction (although by that time Actavis had abandoned its claim in relation to the German designation).

Eli Lilly appealed to the Court of Appeal which upheld the first instance decision in relation to direct infringement but reversed it with respect to indirect infringement, thus finding that Actavis infringed. The Court of Appeal found that if Actavis’ products were reconstituted and/or diluted in a sufficient quantity of saline, the resulting solution would fall within the claims. Both sides applied to the Supreme Court for permission to appeal, but in the meantime the case was remitted by the Court of Appeal to the High Court in order for it to be decided whether, if Actavis markets its product with instructions to reconstitute and/or dilute the products with 5% dextrose solution instead of saline, Actavis would be liable for indirect infringement (the present case).

The present case

The present case relates specifically to Actavis’ pemetrexed diacid product which it launched in the UK in December 2015 and which it submitted it was on track to launch in France, Italy and Spain later in 2016.

When assessing indirect infringement, the Judge held that the relevant question is whether Actavis knew, or it would be obvious to a reasonable person in the circumstances, that Actavis’ pemetrexed diacid product would be diluted in saline by some of Actavis’ customers (disregarding any speculative or maverick use). Actavis adduced unchallenged evidence that it does not know that its pemetrexed diacid product will be diluted in saline, so the Judge had to determine whether this was at least foreseeable. The parties submitted a considerable amount of expert evidence as to the motivation for replacing dextrose with saline. This included evidence from those prescribing and dispensing the drugs as to their likely practices, for example evidence from pharmacists on whether, in the circumstances, and in light of the available stability data, they would be motivated to use saline rather than dextrose. Evidence from foreign law experts was also required, for example in relation to the different legal frameworks in Italy and Spain which regulate switching from the diluents specified in the SmPC to an alternative diluent.

In addition to the question of whether there was a motivation for customers to switch from dextrose to saline, Actavis submitted evidence on the steps it had taken and would take in order to avoid its customers reconstituting and/or diluting with saline. These included sending letters to relevant authorities and medical centres explaining that saline should not be used, having their sales representatives give a similar explanation, having the capability to withdraw supply from customers if Actavis became aware of use or intended use with saline, and not itself releasing stability data on the use of saline. In contrast, the Judge found that there was no evidence that Eli Lilly had taken or was planning to take any steps to prevent use of Actavis’ product with saline.

The Judge concluded that, at the time of his judgment, it was not foreseeable that Actavis’ permetrexed diacid product would be diluted in saline, and accordingly that the DNIs should be granted. This conclusion was reached on the basis that there would be no motivation to use saline rather than dextrose solution to dilute the Actavis product, and that even if there were, it was probable that the steps taken by Actavis to prevent the switch would be effective. The Judge accepted, however, that he could not rule out a future possibility that a change in circumstances would affect the foreseeability of the product being diluted in saline and therefore granted the parties liberty to apply in the event of a material change in circumstances.

Finally, the Judge considered a further issue as to whether letters written by Actavis to Eli Lilly constituted legally binding undertakings not to launch. The Judge held that they did not and, after finding that Actavis had a real commercial interest in obtaining declarations to that effect, granted the declarations.